Skip to main content
Log in

In vitro splenocyte proliferation responses of BALB/c mice to salivary gland extracts of three ixodid tick species (Acari: Ixodidae)

  • Full Paper
  • Published:
Biologia Aims and scope Submit manuscript

Abstract

In vitro proliferation and cytokine production were investigated in BALB/c mice splenic cell cultures that were stimulated with concanavalin A (ConA) and lipopolysaccharide (LPS) and simultaneously exposed to salivary gland extracts (SGE) of unfed and partially fed adult ixodid ticks (Ixodes ricinus, Rhipicephalus appendiculatus, Amblyomma variegatum). Generally, tick SGE enhanced proliferation of unstimulated splenocytes and SGE of unfed ticks suppressed mitogen induced proliferation. Partially fed R. appendiculatus and A. variegatum suppressed ConA responses, while partially fed I. ricinus stimulated both ConA and LPS induced proliferation. A. variegatum and R. appendiculatus females slightly enhanced LPS responses 2 days after attachment but suppressed them at the end of the slow feeding phase. In 72 h ConA induced cell cultures, interferon gamma (IFN-γ) production was suppressed by SGE of all ticks, interleukin (IL)-10 production was enhanced by unfed I. ricinus and partially fed A. variegatum males and IL-5 production was enhanced by feeding R. appendiculatus females and A. variegatum males. The study revealed variability in the responsiveness of murine splenocytes to SGE of different ixodid tick species, whereby patterns of host immunomodulation within one tick species differed between sexes and changed during feeding.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Andrade B.B., Teixeira C.R., Barral A. & Barral-Netto M. 2005. Haematophagous arthropod saliva and host defense system: a tale of tear and blood. Anais da Academia Brasileira de Cięncias 77: 665–693.

    PubMed  CAS  Google Scholar 

  • Anguita J., Ramamoorthi N., Hovius J.W., Das S., Thomas V., Persinski R., Conze D., Askenase P.W., Rincon M., Kantor F.S. & Fikrig E. 2002. Salp15, an Ixodes scapularis salivary protein, inhibits CD4(+) T cell activation. Immunity 16: 849–859.

    Article  PubMed  CAS  Google Scholar 

  • Bergman D.K., Palmer M.J., Caimano M.J., Radolf J.D. & Wikel S.K. 2000. Isolation and molecular cloning of a secreted immunomosuppressant protein from Dermacentor andersoni salivary gland. J. Parasitol. 86: 516–525.

    PubMed  CAS  Google Scholar 

  • Bior A.D., Essenberg R.C. & Sauer J.R. 2002. Comparison of differentially expressed genes in the salivary glands of male ticks, Amblyomma americanum and Dermacentor andersoni. Insect Biochem. Molec. Biol. 32: 645–655.

    Article  CAS  Google Scholar 

  • Bradford M.M. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72: 248–254.

    Article  PubMed  CAS  Google Scholar 

  • Brossard M. & Wikel S.K. 2004. Tick immunobiology. Parasitology 129: S161–S176.

    Article  PubMed  CAS  Google Scholar 

  • Ferreira B.R. & Silva J.S. 1998. Saliva of Rhipicephalus sanguineus tick impairs T cell proliferation and IFN-g-induced macrophage microbicidal activity. Vet. Immunol. Immunopathol. 64: 279–293.

    Article  PubMed  CAS  Google Scholar 

  • Ferreira B.R. & Silva J.S. 1999. Successive tick infestations selectively promote a T-helper 2 cytokine profile in mice. Immunology 96: 434–439.

    Article  PubMed  CAS  Google Scholar 

  • Fuchsberger N., Kita M., Hajnicka V., Imanishi J., Labuda M. & Nuttall P.A. 1995. Ixodid tick salivary gland extracts inhibit production of lipopolysaccharide-induced mRNA of several different human cytokines. Exp. Appl. Acarol. 19: 671–676.

    Article  PubMed  CAS  Google Scholar 

  • Gillespie R.D., Dolan M.C., Piesman J. & Titus R.G. 2001. Identification of an IL-2 binding protein in the saliva of the Lyme disease vector tick, Ixodes scapularis. J. Immunol. 166: 4319–4326.

    PubMed  CAS  Google Scholar 

  • Gillespie R.D., Lamine Mbow M. & Titus R.G. 2000. The immunomodulatory factors of bloodfeeding arthropod saliva. Parasite Immunol. 22: 319–331.

    Article  PubMed  CAS  Google Scholar 

  • Gwakisa P., Yoshihara K., Thanh Long To, Gotoh H., Amano F. & Momotani E. 2001. Salivary gland extract of Rhipicephalus appendiculatus ticks inhibits in vitro transcription and secretion of cytokines and production of nitric oxide by LPS-stimulated JA-4 cells. Vet. Parasitol. 99: 53–61.

    Article  PubMed  CAS  Google Scholar 

  • Hajnická V., Kocáková P., Sláviková M., Slovák M., Gašperík J., Fuchsberger N. & Nuttall P.A. 2001. Anti-interleukin-8 activity of tick salivary gland extracts. Parasite Immunol. 23: 483–489.

    Article  PubMed  Google Scholar 

  • Hajnická V., Vančová I., Kocáková P., Slovák M., Gašperík J., Sláviková M., Hails R.S., Labuda M. & Nuttall P.A. 2005. Manipulation of host cytokine network by ticks: a potential gateway for pathogen transmission. Parasitology 130: 333–342.

    Article  PubMed  Google Scholar 

  • Hannier S., Liversidge J., Sternberg J.M. & Bowman A.S. 2003. Ixodes ricinus tick salivary gland extract inhibits IL-10 secretion and CD69 expression by mitogen-stimulated murine splenocytes and induces hyporesponsiveness in B lymphocytes. Parasite Immunol. 25: 27–37.

    Article  PubMed  CAS  Google Scholar 

  • Hannier S., Liversidge J., Sternberg J.M. & Bowman A.S. 2004. Characterization of the B-cell inhibitory protein factor in Ixodes ricinus tick saliva: a potential role in enhanced Borrelia burgdoferi transmission. Immunology 113: 401–408.

    Article  PubMed  CAS  Google Scholar 

  • Jaworski D.C., Jasinskas A., Metz C.N., Bucala R. & Barbour A.G. 2001. Identification and characterization of a homologue of the proinflammatory cytokine, macrophage migration inhibitory factor in the tick, Amblyomma americanum. Insect Molec. Biol. 10: 323–331.

    Article  CAS  Google Scholar 

  • Kopecký J., Kuthejlová M. & Pechová J. 1999. Salivary gland extract from Ixodes ricinus ticks inhibits production of interferon-g by the upregulation of interleukin-10. Parasite Immunol. 21: 351–356.

    Article  PubMed  Google Scholar 

  • Kovář L., Kopecký J. & Říhová B. 2001. Salivary gland extract from Ixodes ricinus tick polarizes the cytokine profile toward Th2 and suppresses proliferation of T lymphocytes in human PBMC culture. J. Parasitol. 87: 1342–1348.

    Article  PubMed  Google Scholar 

  • Kovář L., Kopecký J. & Říhová B. 2002. Salivary gland extract from Ixodes ricinus tick modulates the host immune response towards the Th2 cytokine profile. Parasitol. Res. 88: 1066–1072.

    Article  PubMed  Google Scholar 

  • Kubeš M., Fuchsberger N., Labuda M., Žuffová E. & Nuttall P.A. 1994. Salivary gland extracts of partially fed Dermacentor reticulatus ticks decrease natural killer cell activity in vitro. Immunology 82: 113–116.

    PubMed  Google Scholar 

  • Kubeš M., Kocáková P., Slovák M., Sláviková M., Fuchsberger N. & Nuttall P.A. 2002. Heterogeneity in the effect of different ixodid tick species on human natural killer cell activity. Parasite Immunol. 24: 23–28.

    Article  PubMed  Google Scholar 

  • Leboulle G., Crippa M., Decrem Y., Mejri N., Brossard M., Bollen A. & Godfroid E. 2002a. Characterization of a novel salivary immunosuppressive protein from Ixodes ricinus ticks. J. Biol. Chem. 277: 10083–10089.

    Article  PubMed  CAS  Google Scholar 

  • Leboulle G., Rochez C., Louahed J., Rutti B., Brossard M., Bollen A. & Godfroid E. 2002b. Isolation of Ixodes ricinus salivary gland mRNA encoding factors induced during blood feeding. Am. J. Trop. Med. Hyg. 66: 225–233.

    PubMed  CAS  Google Scholar 

  • Mejri N., Franscini N., Rutti B. & Brossard M. 2001. Th2 polarization of the immune response of Balb/c mice to Ixodes ricinus instars, importance of several antigens in activation of specific Th2 subpopulations. Parasite Immunol. 23: 61–69.

    Article  PubMed  CAS  Google Scholar 

  • Mejri N., Rutti B. & Brossard M. 2002. Immunosuppressive effects of Ixodes ricinus tick saliva or salivary gland extracts on innate and acquired immune response of BALB/c mice. Parasitol. Res. 88: 192–197.

    Article  PubMed  Google Scholar 

  • Narasimhan S., DePonte K., Marcantonio N., Liang X., Royce T.E., Nelson K.F., Booth C.J., Koski B., Anderson J.F., Kantor F., Fikrig E. 2007. Immunity against Ixodes scapularis salivary proteins expressed within 24 hours of attachment thwarts tick feeding and impairs Borrelia transmission. PLoS ONE 2: e451. doi:10.1371

    Article  PubMed  Google Scholar 

  • Nuttall P.A. & Labuda M. 2004. Tick-host interactions: saliva-activated transmission. Parasitology 129: S177–S189.

    Article  PubMed  CAS  Google Scholar 

  • Ramachandra R.N. & Wikel S.K. 1992. Modulation of host-immune responses by ticks (Acari: Ixodidae)): effects of salivary gland extracts on host macrophages and lymphocyte cytokine production. J. Med. Entomol. 5: 818–826.

    Google Scholar 

  • Rechav Y. & Nuttall P.A. 2000. The effect of male ticks on the feeding performance of immature stages of Rhipicephalus sanguineus and Amblyomma americanum (Acari: Ixodidae). Exp. Appl. Acarol. 24: 569–578.

    Article  PubMed  CAS  Google Scholar 

  • Rolníková T., Kazimírová M. & Buc M. 2003. Modulation of human lymphocyte proliferation by salivary gland extracts of ixodid ticks (Acari: Ixodidae): effect of feeding stage and sex. Folia Parasitol. 50: 305–312.

    PubMed  Google Scholar 

  • Schoeler G.B., Bergman D.K., Manweiler S.K. & Wikel S.K. 2000. Influence of soluble proteins from the salivary glands of ixodid ticks on in-vitro proliferative responses of lymphocytes from BALB/c and C3H/HeN mice. Ann. Trop. Med. Parasitol. 94: 507–518.

    PubMed  CAS  Google Scholar 

  • Schoeler G.B. & Wikel S.K. 2001. Modulation of host immunity by haematophagous arthropods. Ann. Trop. Med. Parasitol. 95: 755–771.

    Article  PubMed  CAS  Google Scholar 

  • Steen N.A., Barker S.C. & Alewood P.F. 2005. Proteins in the saliva of the lxodida (ticks): Pharmacological features and biological significance. Toxicon 47: 1–20.

    Article  PubMed  Google Scholar 

  • Šoltýs J. & Quinn M.T. 1999. Modulation of endotoxin-and enterotoxin-induced cytokine release by in vivo treatment with β-(1,6)-branched β-(1,3)-glucan. Infect. Immun. 67: 244–252.

    PubMed  Google Scholar 

  • Valenzuela J.G., Charlab R., Mather T.N. & Ribeiro J.M. 2000. Purification, cloning, and expression of a novel salivary anti-complement protein from the tick, Ixodes scapularis. J. Biol. Chem. 275: 18717–18723.

    Article  PubMed  CAS  Google Scholar 

  • Wang H., Henbest P.J. & Nuttall P.A. 1999. Successful interrupted feeding of adult Rhipicephalus appendiculatus (Ixodidae) is accompanied by reprogramming of salivary gland protein expression. Parasitology 119: 143–149.

    Article  PubMed  CAS  Google Scholar 

  • Wikel S.K. & Alarcon-Chaidez F.J. 2001. Progress toward molecular characterization of ectoparasite modulation of host immunity. Vet. Parasitol. 101: 275–287.

    Article  PubMed  CAS  Google Scholar 

  • Yu D., Liang J., Yu H., Wu H., Xu C., Liu J. & Lai R. 2006. A tick B-cell inhibitory protein from salivary glands of the hard tick, Hyalomma asiaticum asiaticum. Biochem. Biophys. Res. Comm. 343: 585–590.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mária Kazimírová.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kazimírová, M., Rolníková, T., Dvorožňáková, E. et al. In vitro splenocyte proliferation responses of BALB/c mice to salivary gland extracts of three ixodid tick species (Acari: Ixodidae). Biologia 62, 786–792 (2007). https://doi.org/10.2478/s11756-007-0141-1

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.2478/s11756-007-0141-1

Key words

Navigation